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Removal of Uterus, Ovaries Poses Extra Cardiovascular Risk for Younger Women

— Study highlights need for extra vigilance after hysterectomy and surgical menopause

Ƶ MedicalToday
A photo of surgeons performing a single-site robotic-assisted hysterectomy

A large study supports intensive cardiovascular risk management in women who had undergone hysterectomy, with or without oophorectomy, before natural menopause for reasons other than malignancy.

Findings from the China Kadoorie Biobank show a greater risk of incident cardiovascular disease (CVD) in women who had a hysterectomy alone (adjusted HR 1.09, 95% CI 1.06-1.12) or hysterectomy with bilateral oophorectomy (adjusted HR 1.19, 95% CI 1.12-1.26) compared with peers who did not undergo these procedures, according to Ling Yang, PhD, epidemiologist at the University of Oxford in England, and colleagues.

Additionally, point estimates of CVD risk, estimated over follow-up averaging approximately 10 years, were slightly greater in women who underwent surgery before age 48 years, Yang's group reported in the journal .

Hysterectomy and oophorectomy recipients appeared to have excesses in stroke and ischemic heart disease in particular. There was no difference in hemorrhagic stroke.

"The results of the present study suggest that women who have undergone HBO [hysterectomy with bilateral oophorectomy], but also HA [hysterectomy alone], should be considered for more intensive screening for CVD risk factors, particularly in younger women," the authors urged.

For these patients, hormone replacement therapy may also reduce the risks of atherosclerotic disease due to early loss of endogenous hormones, the group suggested.

CDC estimates that has had a hysterectomy by age 60, though the procedure's popularity has . Surgical removal of the uterus may be accompanied by an oophorectomy that turns off production of estrogen and progesterone, resulting in surgical menopause.

Cardiologist Emily Lau, MD, MPH, of Massachusetts General Hospital and Harvard Medical School in Boston, said the evidence thus far is consistent in showing that women with premature and early menopause, both natural and surgical, are at greater risk for developing CVD later in life. However, the question remains: what is driving the CVD risk for these women?

"Estrogen deficiency -- either due to natural menopause or loss of ovarian function -- has been proposed. What is surprising here is that women who underwent hysterectomy alone with preserved ovarian function still have greater risk of CVD, albeit attenuated compared with women with hysterectomy and bilateral oophorectomy," Lau commented.

"The authors postulate that hysterectomy alone can result in loss of ovarian function via loss of feedback from the uterus to the ovaries, but alternative mechanisms beyond estrogen deficiency should be considered, particularly in light of the landmark that showed that estrogen therapy did not reduce CVD events," she told Ƶ in an email.

More mechanistic studies are needed, but the present study may already have important clinical implications.

"When we are evaluating CVD risk in our women patients, we should absolutely be asking them about their history of hysterectomy and oophorectomy!" Lau stressed.

Yang and colleagues based their study on a biobank that enrolled Chinese women from 2004 to 2008 and then followed them afterward. Their analyses included 282,722 premenopausal women without prior CVD or cancer at enrollment, a group averaging in the early 50s in age at baseline.

There were 8,478 individuals who had undergone a hysterectomy alone, and 1,360 who had hysterectomy with bilateral oophorectomy. Mean age at surgery was 43 years.

Study findings did not appear to support surgical menopause increasing blood levels of total and LDL cholesterol. Compared to women without surgery, these measures were unaffected by hysterectomy alone, and only slightly raised after hysterectomy with bilateral oophorectomy.

However, study investigators warned that cardiovascular risk factors were evaluated only once after the operation and this data may be subject to recall bias and change over time. Details on type of surgery and age at menopause were self-reported as well.

"Indications for hysterectomy were not recorded, but because participants with cancer were excluded from our analysis, we assumed that women underwent hysterectomy for benign indications," Yang's group noted.

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    Nicole Lou is a reporter for Ƶ, where she covers cardiology news and other developments in medicine.

Disclosures

Funding for the study came from the Kadoorie Charitable Foundation, the Wellcome Trust, Chinese National Natural Science Foundation, the National Key Research and Development Program of China, British Heart Foundation, the U.K. Medical Research Council, and Cancer Research U.K.

Yang's group had no disclosures.

Primary Source

Stroke

Poorthuis MHF, et al "Risks of stroke and heart disease following hysterectomy and oophorectomy in Chinese premenopausal women" Stroke 2022; DOI: 10.1161/STROKEAHA.121.037305.